Search PubMed⌕ Search

Biomedical subjects

Y Lebranchu

Publications and source records attributed to Y Lebranchu.

At least 37 records · Page 2Linked to original sources
PubMed2000

Double-blind comparison of two corticosteroid regimens plus mycophenolate mofetil and cyclosporine for prevention of acute renal allograft rejection.

BACKGROUND: Renal transplant recipients experience adverse events attributed to corticosteroid therapy. METHODS: This was a multicenter, randomized, double-blind, 6-month, controlled steroid dose-reduction study in renal transplant recipients with an unblinded 6-month follow-up. In the low/stop arm, corticoste. roids were given at half the dosage of control for 3 months from the date of transplantation, and then withdrawn. Both arms received mycophenolate mofetil and cyclosporine. The primary endpoint was the incidence of biopsy-proven acute rejection at 6 months posttransplantation. RESULTS: There were 248 patients in the control group and 252 in the low/stop group. At 6 months the low/stop group had more biopsy-proven acute rejection episodes than the control (23% vs. 14%; P=0.008). At 12 months this increased to 25% vs. 15%. Most rejections were Banff grade I. Twelve-month graft loss was 5% in the low/stop group vs. 4% in the control. At 6 and 12 months serum cholesterol (P<0.01, P<0.01), triglycer. ides (P<0.01, P<0.01), and systolic blood pressure (P<0.001, P<0.001) were lower in the low/stop group. Diastolic pressure was lower (P<0.01) and lumbar spine bone density was greater (P<0.01) in the low/ stop group at 12 months. CONCLUSIONS: In renal transplant recipients treated with mycophenolate mofetil and cyclosporine, reduction and early withdrawal of the prophylactic corticosteroid dose is feasible without an unacceptable increase in serious rejection episodes. This is accompanied by a significant reduction of steroid-related adverse events.

Adolescent↗
PubMed2000

Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients.

INTRODUCTION: A previous trial in renal transplantation comparing sirolimus (rapamycin) to cyclosporine (CsA) in a triple-drug therapy regimen with azathioprine and corticosteroids found that the incidence of acute rejection was similar (approximately 40%) with a trend for better renal function with sirolimus. METHODS: In 14 European centers, first cadaveric renal allograft recipients were randomized to receive sirolimus (n = 40) or CsA (n = 38) in an open-label design. All patients received corticosteroids and mycophenolate mofetil 2 g/day. Sirolimus and CsA were concentration controlled; trough levels of mycophenolic acid and prednisolone were also measured. RESULTS: At 12 months, graft survival (92.5% sirolimus vs. 89.5% CsA), patient survival (97.5% sirolimus vs. 94.7% CsA), and the incidence of biopsy-proven acute rejection (27.5% sirolimus vs. 18.4% CsA) were not statistically different. The use of antibodies to treat suspected rejection episodes was also similar (7.5% sirolimus vs. 5.3% CsA). More sirolimus patients received bolus steroid therapy (20 vs. 11, P = 0.068). From month 2 onward, the calculated glomerular filtration rate was consistently higher in sirolimus-treated patients. The adverse events reported more frequently with sirolimus were thrombocytopenia (45% vs. 8%) and diarrhea (38% vs. 11%). In the CsA group, increased creatinine (18% vs. 39%), hyperuricemia (3% vs. 18%), cytomegalovirus infection (5% vs. 21%), and tremor (5% vs. 21%) were observed significantly more often. DISCUSSION: Patient and graft survival and the incidence of biopsy-proven acute rejection at 12 months were comparable between sirolimus and CsA, whereas safety profiles were different. These data suggest that sirolimus may be used as primary therapy for the prevention of acute rejection.

Acute Disease↗
PubMed2000

Effects of current smoking and smoking discontinuation on renal function and proteinuria in the general population.

BACKGROUND: Smoking may adversely affect the progression of renal diseases. However, it is unknown whether smoking affects renal function in subjects without nephropathy. METHODS: In 1998, 28,409 volunteers from the general population were examined at the Institut Régional pour la Santé (IRSA). Renal function was estimated with creatinine clearance using the Cockcroft formula. Dipstick proteinuria was assessed on an overnight urine sample by a trained technician. RESULTS: Adjusted creatinine clearance was higher in current smokers than in former smokers and never smokers (100.6 +/- 13.6 vs. 98.8 +/- 13.9 mL/min/1.73 m2, P < 0.0001, and vs. 98.5 +/- 14.0 mL/min/1. 73 m2, P < 0.0001, respectively). This difference was predominant in men and weak in women, and was associated with the number of cigarettes smoked daily. The slope of the projected age-related decline in the creatinine clearance accelerated with age, but it was similar in current smokers, former smokers, and never smokers. Creatinine clearance was associated with a relative risk of proteinuria [for each mL/min/1.73 m2, the relative risk was 1.007 (95% CI, 1.000 to 1.015), P = 0.056, for 1+ or higher proteinuria; and 1.018 (1.004 to 1.030), P = 0.0078, for 2+ or higher proteinuria]. Current and former smokers had a marked risk of 2 or higher proteinuria [adjusted RR (95% CI), 3.26 (1.66 to 6.80), P = 0. 0009, and 2.69 (1.24 to 5.99), respectively, P = 0.013, vs. never smoking], which was independent of the daily or cumulative cigarette consumption. CONCLUSIONS: In the general population, smokers do not exhibit lower creatinine clearance than never smokers. In fact, creatinine clearance is slightly higher in current smokers at least in men, even when normotensive and hypertensive subjects are analyzed separately, but the difference is small, especially in women. This effect seems reversible upon smoking discontinuation. Chronic smoking results in a marked risk of irreversible proteinuria that may occur despite moderate smoking.

Adult↗
PubMed2000

Development of an ex vivo model of pig kidney perfused with human lymphocytes. Analysis of xenogeneic cellular reactions.

BACKGROUND: Because of the explosive nature and the extremely rapid process of hyperacute rejection (HAR), significant infiltration of the xenograft by immunocompetent cells is not observed, and the role and the mechanism of action of cell-mediated rejection in discordant xenografts are therefore still under discussion. METHOD: We developed an experimental approach using pig kidneys perfused with human peripheral blood lymphocytes (PBL) in which the immunologic barrier of hyperacute rejection was excluded and which mimics the in vivo situation. RESULTS: PBL retention in the kidney was evaluated at 20-minute intervals for 3 hours. Retention increased from 30% to 80% with the time of perfusion and was specific because significantly fewer syngeneic lymphocytes were retained. Phenotype analysis of recovered PBL showed a significant decrease in natural killer (NK) cells. Immunohistochemical studies revealed the presence of NK cells and T lymphocytes in the glomerular and interstitial tubular structures of the kidney. Functional studies showed a progressive cessation of diuresis and augmentation of renal vascular resistance when the kidney was perfused with PBL. Electron microscopy examinations of kidney sections perfused with PBL showed swollen endothelial zones, suggesting alterations to and damage of the endothelium. CONCLUSIONS: This system provides a valuable model for the study of early discordant xenogeneic cellular rejection and demonstrates the predominance of xenograft infiltration by NK cells.

Animals↗
PubMed2000

[Anti-pig xenogeneic response by human CD4+ T-lymphocytes].

When considering the hypothesis of xenotransplantation, and if it becomes possible to control hyperacute and delayed vascular rejection, the recognition of porcine graft by human T CD4+ lymphocytes could still constitute a very important barrier. The direct recognition of porcine MHC class II molecules (SLA-DR and SLA-DQ) by human TCR has been demonstrated in vitro. It is accompanied by a proliferative lymphocytic response, as co-stimulatory molecules are able to interact across the species barrier. In vivo, this type of recognition only applies to porcine cells with antigen-presenting functions, mainly the graft dendritic cells which emigrate into the recipient lymphoid organs. The other recognition pathway is indirect, whereby the recipient dendritic cells capture porcine xenoantigens in the graft, then process and present them to the lymphocytes in the lymphoid organs. This indirect pathway can be shown in vitro by utilizing porcine MHC class II-negative endothelial cells. In this model, human purified T CD4+ lymphocyte proliferation is tightly dependent on the presence of human antigen-presenting cells and their HLA class II molecules. As the xenogenic peptides all differ from self peptides, the indirect T-cell response will be very strong and probably difficult to control.

Animals↗
PubMed1999

Fast detection of tissue factor and tissue factor pathway inhibitor messenger RNA in endothelial cells and monocytes by sensitive reverse transcription-polymerase chain reaction.

We developed fast and sensitive reverse transcription-polymerase chain reaction (RT-PCR) procedures to study the expression of tissue factor (TF) and tissue factor pathway inhibitor (TFPI-1) mRNA in human endothelial cells and monocytes. The sensitivity of the technique was checked by performing RT-PCR with limited numbers of cells. Cells were stimulated either with tumor necrosis factor (TNF-alpha) or endotoxin to induce TF mRNA expression or with phorbol ester to increase TFPI-1 mRNA expression. Thus, RT-PCR specific for TF mRNA provided detection from as few as 10(3) TNF-alpha stimulated endothelial cells and 5 x 10(2) monocytes stimulated by endotoxin. TF mRNA expression was increased by TNF-alpha in endothelial cells and in monocytes stimulated by endotoxin. Elevated expression of TF mRNA in monocytes without stimulation by endotoxin was mainly related to cell adhesion. TFPI-1 mRNA was constitutively expressed in endothelial cells and was detected in only 5 x 10(2) unstimulated cells and 10(2) phorbol ester-stimulated cells. Expression was increased upon stimulation with phorbol ester. With this technique, TFPI-1 mRNA in monocytes was rather low even when cells were stimulated with phorbol ester or after adhesion.

Blood Cells↗
PubMed1999

Transplant renal artery stenosis: potential role of ischemia/reperfusion injury and long-term outcome following angioplasty.

PURPOSE: We assess long-term arterial pressure, renal function, and patient and graft survival in recipients of cadaveric kidney transplant with or without transplant renal artery stenosis. We also evaluate the risk factors for transplant renal artery stenosis. MATERIALS AND METHODS: We reviewed and analyzed baseline clinical, immunological and outcome data for 26 patients with transplant renal artery stenosis before and after angioplasty, and 72 without stenosis on angiography. We also analyzed graft and patient survival in 304 cases in which angiography was not performed. RESULTS: The incidence of transplant renal artery stenosis was 6.6% (26 of 402 patients). Acute rejection episodes (42 versus 22%, p <0.05) and delayed graft function (50 versus 32%, p <0.10) were more frequent, and mean cold ischemia time plus or minus standard error (29.2+/-1.7 versus 24.8+/-1.3 hours, p <0.01) was longer in patients with than without transplant renal artery stenosis. The technical success of angioplasty was 92.3%. Restenosis was documented in 6 of 26 patients (23.1%). Revascularization resulted in a decrease in arterial pressure and better renal function. The 8-year patient (100, 98.6 and 95.7%, respectively) and graft (88.1, 88.9 and 89.3%, respectively) actuarial survival rates were similar among patients with or without transplant renal artery stenosis, and those who did not undergo angiography. CONCLUSIONS: Transplant renal artery stenosis had no detectable influence on long-term arterial pressure control, renal function, and patient and graft survival rates, which were similar to those in patients without stenosis. Long cold ischemia time may have a role in the development of transplant renal artery stenosis through ischemia/reperfusion injury.

Adult↗
PubMed1999

[Can man live with a pig kidney?].

The transplantation of organs from one species to another introduces a question of compatibility not seen in allotransplantation, the ability of a kidney to perform its physiological function in the new host environment. It has been assumed that an allotransplanted organ will function normally if is not rejected; ample experience supports this assumption. This luxury will not exist in the field of xenotransplantation, where the issues of comparative physiology will assume great importance. From many standpoints, the pig kidney seems an ideal donor for xenotransplantation. They are of similar size and have remarkably similar internal anatomy. Even if the immunological problems could be overcome, there is almost no direct experimental evidence to answer the question of whether or not a pig kidney can function in a human body.

Animals↗
PubMed1998

Human T lymphocyte proliferative response to resting porcine endothelial cells results from an HLA-restricted, IL-10-sensitive, indirect presentation pathway but also depends on endothelial-specific costimulatory factors.

To investigate the mechanisms of cellular rejection in pig-to-human xenotransplantation, the proliferation of different human purified lymphocyte subpopulations in response to swine leukocyte Ag class II-negative porcine aortic endothelial cells (PAEC) was measured in the presence or absence of human autologous adherent cells (huAPC). CD8+ lymphocytes proliferated moderately in the absence of huAPC, and the immune response was slightly increased when huAPC were added. CD56+ lymphocytes failed to proliferate in response to PAEC whether huAPC were present or not. CD4+ lymphocytes alone did not proliferate in response to PAEC, but a strong proliferative response was observed in the presence of metabolically active huAPC. This response was totally abolished by mAbs directed against HLA class II molecules or by pretreatment of huAPC by human IL-10. Even in the presence of huAPC, CD4+ lymphocytes failed to respond to fixed PAEC or to PAEC-lysates, suggesting that PAEC must be viable to support lymphocyte proliferation. Finally, none of the nonendothelial porcine adherent cells tested was able to induce human lymphocyte proliferation, despite the fact that they also provided a large set of xenogeneic peptides. Our results show that the indirect presentation pathway of xenoantigens by huAPC to CD4+ lymphocytes is crucial in the response to porcine endothelial cells, and that IL-10 could be of therapeutic interest to prevent human lymphocyte activation by this pathway. Furthermore, we demonstrated that stimulatory signals specifically provided by endothelial cells are also necessary for this huAPC-restricted proliferative response.

Animals↗
PubMed1998

Human allogeneic lymphocytes trigger endothelial cell tissue factor expression by a tumor necrosis factor-dependent pathway.

Lymphocyte adhesion to endothelial cells and the extravascular deposition of fibrin are 2 important processes during pathologic situations such as allograft rejection. Tissue factor (TF) expression was therefore measured on human umbilical vein endothelial cells (HUVECs) after coculture with allogeneic lymphocytes (PBLs) by a factor Xa generation assay. When cocultured with PBLs, HUVECs expressed strong procoagulant activity related to the TF/factor VII-dependent pathway, which was enhanced when endothelial cells were treated with interferon-gamma (IFN-gamma). The highest TF activity was measured when 10(5) lymphocytes were incubated with 10(4) HUVECs (ratio 10: 1) for 4 hours, a time-dependent course similar to that obtained with tumor necrosis factor-alpha (TNF-alpha), and direct contact between the 2 cell types was necessary. PBL-induced TF activity was inhibited by cycloheximide or actinomycin D, indicating active protein synthesis that was confirmed by the increase in TF mRNA detected by reverse transcription-polymerase chain reaction. It was then demonstrated that 1 of the primary signaling pathways leading to endothelial cell TF expression was a rapid initial interaction between membrane TNF expressed on PBLs and the 75-kd TNF receptor, with subsequent involvement of platelet-activating factor and P-selectin. Finally, we showed that the transduction of external signals involving the activation of protein kinase C and protein tyrosine kinases also contributed to the regulation of TF expression.

Cells, Cultured↗